Study Purpose. Health status is determined by inputs at both the individual and community level. Racial residential segregation (RRS) is a community attribute proposed to influence health and health status. Yet its effects may be correlated with and mediated by characteristics of communities and their residents. The extent to which RRS influences health and the pathways through which it exerts effects have not been fully explored. This study will: 1) determine the independent effect of several global and local RRS measures in explaining changes in health status after adjusting for community and individual-level effects;2) specify pathways and mechanisms by which these RRS measures influence change in health using community and individual level mediating factors;and 3) compare the relative explanatory power of these RRS measures and determine whether the mediation mechanisms vary across these measures. Methods: Nationally representative data from the Health and Retirement Study, a large prospective cohort study of approximately 4690 white, 1198 black and 590 Hispanic adults 51 to 61 years of age at enrollment will be merged with data from the Area Resource File and US Census. Guided by our conceptual model, we will develop operational measures for economic, social, physical and health system community characteristics potentially located on the path between RRS and health status. We use spatial and aspatial measures, both two-group (black/white or Hispanic/white) and multi-group (white/black/Hispanic) design, determined at the global (i.e., metropolitan or city) and the local or census tract level. Measures of individual-level SES, health behaviors, and chronic conditions will be included in our model. We will examine the relationship between RRS and health using the following health outcomes based on self-reports of 1) a major decline, no change, or improvement in health from 1992 to 2002;2) a major decline or death, no change, or improvement in health from 1992 to 2002;3) a continuous measure using transformed values of the self-reports including death;and 4) changes in physical limitations in a) mobility, b) agility, or c) facility between 1992 and 2000. Race/ethnicity-stratified hierarchical/multilevel modeling and logistic regression will be used to assess the association between RRS and health status, after controlling for community and individual-level characteristics. Race/ethnicity-stratified structural equation modeling will be used to delineate the mediating pathways between RRS, community and individual-level characteristics, and health status. Significance: The current proposal is one of the first studies to use longitudinal data to explore potential causal pathways between RRS and health. Understanding mediation and moderation in these pathways will advance our current understanding of the importance of community level factors on health and will re-focus policy decisions on the need for interventions that address these fundamental causes of disparities in health status.